Objective Motor neurons (MNs) constitute the final common pathway in the generation of behaviors by linking the CNS with the movement apparatus. Herein, MNs diversify into fast, intermediate and slow types whose properties are tuned to the speed, force and endurance of the muscle fiber contractions they elicit. The MN-muscle fiber units display marked plasticity towards chronically altered physical activity, and show strong differences in their vulnerability towards degenerative conditions affecting the neuromuscular system, including amyotrophic lateral sclerosis and aging. Despite their central importance for determining neuromuscular output, plasticity and vulnerability the molecular mechanisms determining the functional MN types remain unknown. My group will use a cross-disciplinary approach by employing molecular genetic, cell biological, electrophysiological and motor behavior assays in mouse and chick to dissect molecular pathways determining MN type status and their contribution to neuromuscular system function and plasticity. Based on our preliminary data, this will focus on the contribution of non-canonical Notch signaling to MN type-specification and neuromuscular function, in addition to four newly identified neural activity modulators as candidate effectors of motor unit output and plasticity. This will be complemented by screening additional pathway components for roles in determining MN type properties through newly developed rapid gene tagging and electrophysiological interrogation in chick, followed by addressing their requirement for motor unit specification and function in mouse. Through an iterative cycle of (i) investigating candidate determinants of motor unit type, (ii) defining their role and mode of action in motor unit specification and function in the context of the neuromuscular system, and (iii) identifying essential downstream components, the proposal will explore molecular pathways operating in motor unit specification, function and plasticity. Fields of science medical and health sciencesbasic medicineneurologyamyotrophic lateral sclerosis Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-SG-LS5 - ERC Starting Grant - Neurosciences and neural disorders Call for proposal ERC-2012-StG_20111109 See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Host institution UNIVERSITAETSKLINIKUM AACHEN EU contribution € 202 789,64 Address Pauwelsstrasse 30 52074 Aachen Germany See on map Region Nordrhein-Westfalen Köln Städteregion Aachen Activity type Higher or Secondary Education Establishments Administrative Contact Volker Legewie (Mr.) Principal investigator Till Marquardt (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (2) Sort alphabetically Sort by EU Contribution Expand all Collapse all UNIVERSITAETSKLINIKUM AACHEN Germany EU contribution € 202 789,64 Address Pauwelsstrasse 30 52074 Aachen See on map Region Nordrhein-Westfalen Köln Städteregion Aachen Activity type Higher or Secondary Education Establishments Administrative Contact Volker Legewie (Mr.) Principal investigator Till Marquardt (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data UNIVERSITAETSMEDIZIN GOETTINGEN - GEORG-AUGUST-UNIVERSITAET GOETTINGEN - STIFTUNG OEFFENTLICHEN RECHTS Participation ended Germany EU contribution € 1 254 017,36 Address Robert-Koch-Strasse 40 37075 Goettingen See on map Region Niedersachsen Braunschweig Göttingen Activity type Higher or Secondary Education Establishments Administrative Contact Christiane Hennecke (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
